Evaluating breast ultrasonography as a complementary diagnostic method in girls with central precocious puberty.

BACKGROUND: Assessment of breast development by physical examination can be difficult in the early stages and in overweight girls. OBJECTIVE: To investigate ultrasonography (US) for evaluation of early breast development. MATERIALS AND METHODS: In a prospective study, 125 girls (age 7.1 ± 1.5 years) with breast development before 8 years underwent US breast staging, breast volume, and elastography, in addition to clinical/hormonal evaluation for precocious puberty. Accuracy of US for determining breast development and predicting progression to central precocious puberty was investigated. RESULTS: Physical examination revealed glandular breast enlargement in 100 and predominantly lipomastia in 25. Breast US in the former confirmed glandular breast development in 92 (group 1, physical examination and US positive), but not in 8 (group 2, physical examination positive, US negative). Comparison of the two groups demonstrated lower Tanner and US staging, bone age/chronological age, basal luteinizing hormone (LH), breast volume, and uterine volume in group 2. In the 25 lipomastia patients, US demonstrated no breast tissue in 19 (group 3, physical examination and US negative), but US stage ≥ II in 6 (group 4, physical examination negative, US positive) without differences in clinical parameters. After follow-up of 19.8 ± 4.2 months, 46/125 subjects were diagnosed with precocious puberty. US stage, total breast volume, and shear-wave speeds were significantly higher in these 46 patients. Multivariate analyses demonstrated breast volume > 3.4 cc had odds ratio of 11.0, sensitivity of 62%, and specificity of 89, in predicting progression to precocious puberty, being second only to stimulated LH for all variables. CONCLUSION: Breast US is a useful predictive tool for diagnosis of precocious puberty in girls. Higher US stages and higher breast volume on US increased the likelihood of eventual diagnosis of precocious puberty.

Bone Phenotype is Always Present But Androgen Excess is Less Frequently Seen in PAPSS2 Deficiency

3'-Phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) deficiency is a rare disorder due to biallelic pathogenic variants in the PAPSS2 gene. This disorder was first described in 1998 by Ahmad et al. and Faiyaz ul Haque et al. To date, 79 patients with PAPSS2 deficiency have been reported. The main reported features of these patients are related to bone abnormalities and clinical/biochemical androgen excess. Disproportionate short stature and symptoms associated with spondylar skeletal dysplasia are the most common clinical features that require clinical attention. Androgen excess has been described much less commonly. This review summarizes the currently published clinical, molecular, and biochemical features of patients with PAPSS2 deficiency.

Development of external genitalia during mini-puberty: is it related to somatic growth or reproductive hormones?

Although hypothalamo-pituitary-gonadal axis is active during mini-puberty, its relationship with somatic growth and the role on the development of external genitalia has not been fully elucidated. We aimed to evaluate the effects of somatic growth and reproductive hormones on the development of external genitalia during mini-puberty. Anthropometric data, pubertal assesment, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), sex-hormone binding globulin (SHBG), estradiol (E2) and inhibin-B, testosterone (T), and anti-Mullerian Hormone (AMH) of healthy infants aged 1-4 months were evaluated. Free sex hormone index was calculated as T/SHBG for boys and E2/SHBG for girls. The mean age of 148 (74 female) infants included in the study was 2.31 ± 0.76 months. Tanner stage 2-3 sex steroid and gonadotropin levels were observed. A statistically significant difference was found between the weight, height, BMI, weight gain and serum FSH, LH, and A4 measurements of girls and boys (p < 0.05). Penile length was associated with weight (r = 0.24, p = 0.03), height (r = 0.25, p = 0.02), and AMH (r = 0.3, p = 0.01), but not with testosterone (p = 0.56 respectively). A negative correlation was found between weight and serum LH (r = - 0.26, p = 0.2) and T/SHBG levels in males (r = - 0.38, p = 0.015 respectively). Weight-SDS was negatively correlated with testosterone in males (r = - 0.25, p = 0.02). Testicular size and breast stage did not correlate with any of the hormonal and anthropometric parameters.  Conclusions: External genitalia in males during mini-puberty is related more to somatic growth rather than reproductive hormones. Similar to pubertal developmental stages, both total and free testosterone are negatively associated with higher weight during mini-puberty. What is Known: • Mini-puberty allows early assessment of HPG axis function in infancy. • There is an inverse relationship between the amount of adipose tissue and circulating testosterone levels in males during puberty and adulthood. • The potential effect of somatic growth and reproductive hormones on external genital development during mini-puberty remains unclear. What is New: • During mini-puberty, males' external genitalia is more related to somatic growth than to reproductive hormones, but this relationship is not observed in girls. • Both total and free testosterone are negatively associated with higher weight during mini-puberty, similar to the pubertal developmental stages.

Challenges in the Management of a 7-Year-Old Child with Thyrotropin-Secreting Pituitary Adenoma and the Review of the Literature.

INTRODUCTION: Thyrotropin-producing pituitary adenoma (TSHoma) is a very rare disease, representing less than 1% of the pituitary tumours and presenting with elevated thyroid hormones and normal/high TSH concentrations. CASE PRESENTATION: A 7-year-old boy with nervousness was referred by his psychiatrist for elevated free T4, T3, and TSH levels. Initial evaluation revealed an elevated α-subunit. Pituitary magnetic resonance imaging (MRI) demonstrated a macroadenoma. The patient underwent a trans-sphenoidal tumour resection (TSS) which showed positive immunohistochemical staining for TSH, growth hormone, and prolactin in tumoral tissue. Euthyroidism was achieved for 1 year after TSS, then recurrence of tumour with elevated TSH and thyroid hormone levels necessitated a re-operation with TSS followed by gamma-knife radiosurgery. The euthyroid state was achieved and lasted for 2.5 years this time, but due to the recurrence, medical treatment had been commenced with cabergoline and octreotide. Euthyroidism was maintained for the last 4 years on monthly octreotide treatment. A repeat MRI demonstrated no pituitary mass, but a mass in the sphenoidal sinus had been detected. Removal of this mass by surgery did not achieve euthyroidism. 68Ga-DOTA-TATE positron emission tomography/computed tomography showed residual tissue extending from the pituitary region to the sphenoid sinus. The patient's bone age was advanced by 2 years at diagnosis which became 4 years in 1 year after the diagnosis and remained so throughout follow-up, leading to a final height of -3.3 SDS below his target height at the age of 16 years. CONCLUSION: The diagnosis, treatment, and follow-up of TSHomas are challenging, and short stature due to accelerated bone maturation is a complication of paediatric TSHomas.

Cranial MRI Abnormalities and Long-term Follow-up of the Lesions in 770 Girls With Central Precocious Puberty.

CONTEXT: Central precocious puberty (CPP) may arise from central nervous system (CNS) lesions in a few affected girls. Recently, the incidence of girls with CPP has increased mostly in 6-8 year olds, in whom the necessity of magnetic resonance imaging (MRI) is debated. OBJECTIVE: To investigate the frequency, long-term outcome and potential predictors of CNS lesions in a large cohort of girls with CPP. METHODS: A multicenter cohort of 770 Turkish girls with CPP who had systematic cranial MRI between 2005 and 2017. Age at puberty onset was <6 years in 116 and 6-8 years in 654. CNS lesions were followed until final decision(6.2 ± 3.1 years). Potential predictors of CNS lesions were evaluated by univariate analyses. RESULTS: A total of 104/770 (13.5%) girls had abnormal brain MRI. Of these, 2.8% were previously known CNS lesions, 3.8% had newly detected and causally related CNS lesions, 3.1 % were possibly, related and 3.8% were incidental. Only 2 (0.25%) neoplastic lesions (1 low grade glioma and 1 meningioma) were identified; neither required intervention over follow-up of 6 and 3.5 years respectively. Age at breast development <6 years (odds ratio [OR] 2.38; 95% CI 1.08-5.21) and the peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio >0.6 (OR 3.13; 95% CI 1.02-9.68) were significantly associated with CNS lesions. However, both patients with neoplastic lesions were >6 years old. CONCLUSION: Although age and LH/FSH ratio are significant predictors of CNS lesions, their predictive power is weak. Thus, systematic MRI seems to be the most efficient current approach to avoid missing an occult CNS lesion in girls with CPP, despite the low likelihood of finding a lesion requiring intervention.